scholarly journals The PU.1-Regulated Long Noncoding RNA Lnc-MC Controls Human Monocyte/Macrophage Differentiation through Interaction with MicroRNA-199a-5p

2015 ◽  
pp. MCB.00429-15 ◽  
Author(s):  
Ming-Tai Chen ◽  
Hai-Shuang Lin ◽  
Chao Shen ◽  
Yan-Ni Ma ◽  
Fang Wang ◽  
...  
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Human Monocyte ◽  
Regulation Mechanism ◽  
Loss Of Function ◽  
Macrophage Differentiation ◽  
Hematopoietic Stem ◽  
Mechanistic Investigation ◽  
Repressive Effect

Long noncoding RNAs (lncRNAs) are emerging as important regulators in mammalian development, but little is known about their roles in monocyte/macrophage differentiation. Here we identified a long noncoding RNA MonoCyte (lnc-MC), which exhibits increased expression during monocyte/macrophage differentiation of THP-1 and HL-60 cells as well as CD34+hematopoietic stem/progenitor cells (HSPCs), and is transcriptionally activated by PU.1. Gain and loss of function assays demonstrate that lnc-MC promotes monocyte/macrophage differentiation of THP-1 cells and CD34+HSPCs. Mechanistic investigation reveals that lnc-MC acts as a competing endogenous RNA to sequester miR-199a-5p and alleviate repression on activin A receptor type 1B (ACVR1B) expression, an important regulator of monocyte/macrophage differentiation. We also noted repressive effect of miR-199a-5p on lnc-MC expression and function, but PU.1-dominant down-regulation of miR-199a-5p results in its adverse position in the reciprocal regulation between miR-199a-5p and lnc-MC. Altogether, our work uncovers that PU.1-regulated two noncoding RNAs, lnc-MC and miR-199a-5p, have opposing roles in monocyte/macrophage differentiation and during the differentiation lnc-MC further enforces PU.1's role to facilitate the process by sponging miR-199a-5p and releasing ACVR1B expression, which confers a novel regulation mechanism composed of PU.1, lnc-MC, miR-199a-5p and ACVR1B in the monocyte/macrophage differentiation.

scholarly journals The long noncoding RNA lncPARP1 contributes to progression of hepatocellular carcinoma through up-regulation of PARP1

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Heqiang Qi ◽  
Yuyan Lu ◽  
Jie Lv ◽  
Huita Wu ◽  
Jing Lu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
Human Cancer ◽  
Noncoding Rnas ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Mechanistic Investigation ◽  
Induced Apoptosis ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) accounts for a large proportion of cancer-associated mortality worldwide. The functional impact of long noncoding RNAs (lncRNAs) in human cancer is not fully understood. Here, we identified a novel oncogenic lncRNA termed as lncPARP1, which was significantly up-regulated in HCC. Increase in lncPARP1 expression was associated with age, α-fetoprotein (AFP) levels, tumor size, recurrence, and poor prognosis of HCC patients. Loss-of-function approaches showed that knockdown of lncPARP1 inhibited proliferation, migration, and invasion, while induced apoptosis in HCC cells. Moreover, mechanistic investigation demonstrated that PARP1 was an underlying target of lncPARP1 in HCC. In summary, we provide the first evidence that lncPARP1 exerts an oncogene to promote HCC development and progression, at least in part, by affecting poly (ADP-ribose) (PAR) polymerase 1 (PARP1) expression.

THU0078 EXPRESSION PROFILE ANALYSIS OF LONG NONCODING RNAS INDUCED BY IL-1ß IN RHEUMATOID ARTHRITIS FIBROBLAST-LIKE SYNOVIOCYTES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 251.1-251
Author(s):  
J. M. Kim ◽  
H. J. Kang ◽  
S. J. Jung ◽  
B. W. Song ◽  
H. J. Jeong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Expression Profile ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Aberrant Expression ◽  
Iκb Kinase ◽  
Ngs Data ◽  
Fibroblast Like Synoviocytes

Background:Long noncoding RNAs (lncRNAs) have recently emerged as important biological regulators and the aberrant expression of lncRNAs has been reported in various diseases including cancer, cardiovascular disease, and diabetes mellitus. However, the role of lncRNAs in the pathogenesis of rheumatoid arthritis (RA) remains unknown.Objectives:Thus, we studied lncRNAs influenced by IL-1, which is one of the key mediators in the pathogenesis of RA, and also investigated whether regulation of NF-κB activation, which is known to be induced by IL-1, could lead to the changes of expression of those lncRNAs.Methods:Fibroblast-like synoviocytes (FLS) were obtained from the knee joints of the patients with RA. The next-generation sequencing (NGS) data were analyzed to identify differentially expressed lncRNAs between unstimulated RA FLS and IL-1-stimulated RA FLS. The expression levels of the top 5 candidates in NGS data were validated by RT-qPCR using extended number of unstimulated RA FLS and IL-1-stimulated RA FLS. IMD-0560, an inhibitor of IκB kinase (IKK) was used for the regulation of NF-κB activation. Activation and inhibition of NF-κB were confirmed by Western blotting. Changed expressions of the lncRNAs were identified by RT-qPCR.Results:NGS analysis revealed up-regulated 30 lncRNAs and down-regulated 15 lncRNAs in IL-1-treated RA FLS compared with unstimulated RA FLS. Top 5 lncRNAs were selected among 30 lncRNAs up-regulated by IL-1 in RA FLS based on fold-change with P-value cutoff. The up-regulated lncRNAs including NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 were validated by RT-qPCR. IMD-0560 inhibited phosphorylation of IκBα induced by IL-1 in RA FLS. Overexpression of lncRNAs induced by IL-1 was also inhibited by IMD-0560 in RA FLS.Conclusion:Our study revealed that IL-1 increased the expression of NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 in RA FLS. In addition, the expression of these lncRNAs was regulated by inhibition of NF-κB activation. Thus, our data suggest that the lncRNAs might be involved in the pathogenesis of RA through NF-κB signaling pathway.References:[1]Long noncoding RNAs and human disease. Trends Cell Biol. 2011 Jun;21(6):354-61.[2]A long noncoding RNA mediates both activation and repression of immune response genes. Science. 2013 Aug 16;341(6147):789-92.[3]Long noncoding RNA expression profile in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Res Ther. 2016 Oct 6;18(1):227.Disclosure of Interests:None declared

scholarly journals Long noncoding RNA SNHG25 promotes the malignancy of endometrial cancer by sponging microRNA-497-5p and increasing FASN expression

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuhua He ◽  
Shuifang Xu ◽  
Yi Qi ◽  
Jinfang Tian ◽  
Fengying Xu
Keyword(s):  
Endometrial Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Study Cohort ◽  
Loss Of Function ◽  
Ec Cells

Abstract Background Small nucleolar RNA host gene 25 (SNHG25), a long noncoding RNA, has been well-studied in epithelial ovarian cancer. However, the specific functions of SNHG25 in endometrial cancer (EC) have not been studied yet. In this study, we aimed to elucidate the clinical significance of SNHG25 in EC and determine the regulatory activity of SNHG25 on the tumor-associated EC phenotype. We also thoroughly explored the molecular mechanisms underlying SNHG25 function in EC. Methods Gene expression was measured using quantitative real-time polymerase chain reaction. The detailed functions of SNHG25 in EC were examined by performing loss-of-function experiments. Moreover, the regulatory mechanisms involving SNHG25, microRNA-497-5p, and fatty acid synthase (FASN) were unveiled using the luciferase reporter assay and RNA immunoprecipitation. Results We observed a high level of SNHG25 in EC using the TCGA dataset and our study cohort. Patients with a high SNHG25 level had shorter overall survival than those with a low SNHG25 level. SNHG25 deficiency resulted in tumor-repressing activities in EC cells by decreasing cell proliferation, migration, and invasion and promoting cell apoptosis. Furthermore, the function of SNHG25 depletion in impairing tumor growth in vivo was confirmed. SNHG25 sequestered miR-497-5p as a competing endogenous RNA in EC and consequently positively regulated FASN expression. Thus, the decrease in miR-497-5p or increase in FASN could neutralize the modulatory actions of SNHG25 knockdown in EC cells. Conclusions The depletion of SNHG25 impedes the oncogenicity of EC by targeting the miR-497-5p/FASN axis. The newly elucidated SNHG25/miR-497-5p/FASN pathway may be a promising target for the molecular-targeted management of EC.

Knockdown of long noncoding RNA AC245100.4 inhibits the tumorigenesis of prostate cancer cells via the STAT3/NR4A3 axis

Epigenomics ◽  
2021 ◽  
Author(s):  
Chi Liu ◽  
Ping Lin ◽  
Jiabin Zhao ◽  
Hui Xie ◽  
Rou Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Rna Sequencing ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Transcriptional Repressor ◽  
Sequencing Analysis ◽  
Loss Of Function ◽  
Prostate Cancer Cells ◽  
Rna Immunoprecipitation

Aim: To explore the role and mechanism of long noncoding RNA AC245100.4 and NR4A3 in prostate cancer (PCa). Methods: RNA-sequencing analysis was used to detect the downstream genes of AC245100.4. A series of gain- and loss-of-function approaches were used to investigate the roles of AC245100.4 and NR4A3. RNA immunoprecipitation was performed to examine the interaction between AC245100.4 and STAT3. Results: AC245100.4 was significantly upregulated in PCa cells and tissues. Knockdown of AC21500.4 significantly inhibited the tumorigenesis of PCa cells. Mechanistically, AC245100.4 deregulated the transcription of NR4A3 via increasing p-STAT3, which acted as a transcriptional repressor of NR4A3. Conclusion: Knockdown of lncRNA AC245100.4 inhibits the tumorigenesis of PCa cells via the STAT3/ NR4A3 axis.

scholarly journals Long noncoding RNA ANRIL protects cardiomyocytes against hypoxia/reoxygenation injury by sponging miR-195-5p and upregulating Bcl-2

RSC Advances ◽  
2019 ◽  
Vol 9 (61) ◽  
pp. 35624-35635 ◽  
Author(s):  
Hui Zhao ◽  
Li Meng ◽  
Chengyang Xu ◽  
Bin Lin ◽  
Xiangming Zheng ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Reoxygenation Injury ◽  
Hypoxia Reoxygenation

Long noncoding RNAs have been widely accepted to play important roles in acute myocardial infarction (AMI).

scholarly journals Silencing of Long Noncoding RNA Nespas Aggravates Microglial Cell Death and Neuroinflammation in Ischemic Stroke

Stroke ◽  
2019 ◽  
Vol 50 (7) ◽  
pp. 1850-1858 ◽  
Author(s):  
Yiming Deng ◽  
Duanduan Chen ◽  
Luyao Wang ◽  
Feng Gao ◽  
Bo Jin ◽  
...  
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Oxygen Glucose Deprivation ◽  
Cerebral Artery Occlusion

Background and Purpose— Ischemic stroke is one of the leading causes of morbidity and mortality worldwide and a major cause of long-term disability. Recently, long noncoding RNAs have been revealed, which are tightly associated with several human diseases. However, the functions of long noncoding RNAs in ischemic stroke still remain largely unknown. In the current study, for the first time, we investigated the role of long noncoding RNA Nespas in ischemic stroke. Methods— We used in vivo models of middle cerebral artery occlusion and in vitro models of oxygen-glucose deprivation to illustrate the effect of long noncoding RNA Nespas on ischemic stroke. Results— We found expression of Nespas was significantly increased in ischemic cerebral tissues and oxygen-glucose deprivation–treated BV2 cells in a time-dependent manner. Silencing of Nespas aggravated middle cerebral artery occlusion operation–induced IR injury and cell death. In addition, proinflammatory cytokine production and NF-κB (nuclear factor-κB) signaling activation were inhibited by Nespas overexpression. TAK1 (transforming growth factor-β–activated kinase 1) was found to directly interact with Nespas, and TAK1 activation was significantly suppressed by Nespas. At last, we found Nespas-inhibited TRIM8 (tripartite motif 8)-induced K63-linked polyubiquitination of TAK1. Conclusions— We showed that Nespas played anti-inflammatory and antiapoptotic roles in cultured microglial cells after oxygen-glucose deprivation stimulation and in mice after ischemic stroke by inhibiting TRIM8-related K63-linked polyubiquitination of TAK1.

Implication of regulatory networks of long noncoding RNA/circular RNA-miRNA-mRNA in diabetic cardiovascular diseases

Epigenomics ◽  
2020 ◽  
Vol 12 (21) ◽  
pp. 1929-1947
Author(s):  
Wei Xiong ◽  
Mengran Yao ◽  
Yuqiao Yang ◽  
Yan Qu ◽  
Jinqiao Qian
Keyword(s):  
Diabetes Mellitus ◽  
Cardiovascular Diseases ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Regulatory Networks ◽  
Noncoding Rnas ◽  
Circular Rna ◽  
Competing Endogenous Rna ◽  
Prognostic Evaluation ◽  
Functional Roles

Diabetic cardiovascular diseases (DCVDs) are the most common complications of diabetes mellitus and are considered to be one of the most important threats to global health and an economic burden. Long noncoding RNA (lncRNA), circular RNA (circRNA), and miRNA are a novel group of noncoding RNAs that are involved in the regulation of various pathophysiological processes, including DCVDs. Interestingly, both lncRNA and circRNA can act as competing endogenous RNA of miRNA, thereby regulating the expression of the target mRNA by decoying or sponging the miRNA. In this review, we focus on the mechanistic, pathological and functional roles of lncRNA/circRNA-miRNA-mRNA networks in DCVDs and further discuss the potential implications for early detection, therapeutic intervention and prognostic evaluation.

scholarly journals Long Noncoding RNA Plays a Key Role in Metastasis and Prognosis of Hepatocellular Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Guangbing Li ◽  
Haohai Zhang ◽  
Xueshuai Wan ◽  
Xiaobo Yang ◽  
Chengpei Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Comprehensive Review ◽  
Cellular Processes

Long noncoding RNAs (lncRNAs) have been attracting immense research interests. However, only a handful of lncRNAs had been thoroughly characterized. They were involved in fundamental cellular processes including regulation of gene expression at epigenetics as well as tumorogenesis. In this paper, we give a systematic and comprehensive review of existing literature about lncRNA involvement in hepatocellular carcinoma. This review exhibited that lncRNAs played important roles in tumorigenesis and subsequent prognosis and metastasis of hepatocellular carcinoma and elucidated the role of some specific lncRNAs such as MALAT1 and HOTAIR in the pathophysiology of hepatocellular carcinoma and their potential of being therapeutic targets.

scholarly journals Transcriptomes Analysis Reveals the Regulatory Roles of Noncoding RNA in Tanshinones Synthesis Pathway of Salvia Miltiorrhiza

2021 ◽  
Author(s):  
Caicai Lin ◽  
Changhao Zhou ◽  
Zhongqian Liu ◽  
Xingfeng Li ◽  
Zhenqiao Song
Keyword(s):  
Noncoding Rna ◽  
Target Genes ◽  
Salvia Miltiorrhiza ◽  
Expression Patterns ◽  
Noncoding Rnas ◽  
Synthesis Process ◽  
Circular Rnas ◽  
Regulation Mechanism ◽  
Pentatricopeptide Repeat ◽  
Specific Expression

Abstract Background: Long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) have been shown to play fundamental roles in plant development. However, the information of these noncoding RNAs (ncRNAs) in Salvia miltiorrhiza remains largely unexplored. In this study, the expression pattern of ncRNAs in six tissues from the same strain of S. miltiorrhiza was analyzed to study the biological function of ncRNAs on active ingredients synthesis.Methods: Analysis of tanshinone content differences of two root simples was carried out on high-performance liquid chromatography (HPLC). RNA sequencing, GO and KEGG enrichment analysis were applied to analyzing the targets of diferentially expressed ncRNAs in different organs.Results: A total of 6,929 lncRNAs, 6,239 circRNAs, and 360 miRNAs were identified. Forty-eight lncRNAs, 70 miRNAs, and 26 circRNAs expressed differentially between red and white root tissues with significantly different tanshinone content. GO and KEGG pathway analysis of target genes of differently expressed ncRNAs indicated that some target genes are involved in the synthesis pathway of terpene, including diterpene and sesquiterpene. We also found many target genes related to secondary metabolites, including 2-C-Methyl-d-erythritol 2,4-cyclodiphosphate Synthase (SmMCS) and several CYP450s. Furthermore, most target genes may be related to the resistance of pathogens, such as receptor kinases, disease-resistant proteins, and pentatricopeptide repeat-containing proteins. Conclusions: The present study exhibited the tissue-specific expression patterns of ncRNAs preliminarily in S. miltiorrhiza, which may reflect that the formation of white root or red root is related to regulation by ncRNAs. It would provide a basis for further research about the regulation mechanism in the tanshinone synthesis process.

scholarly journals Myeloid leukemia vulnerabilities at CTCF-enriched long noncoding RNA loci

2021 ◽  
Author(s):  
Michelle Ng ◽  
Lonneke Verboon ◽  
Hasan Issa ◽  
Raj Bhayadia ◽  
Oriol Alejo-Valle ◽  
...  
Keyword(s):  
Long Noncoding Rna ◽  
Myeloid Leukemia ◽  
Noncoding Rna ◽  
K562 Cells ◽  
Cell Types ◽  
Clinical Aspects ◽  
Hematopoietic Stem ◽  
Regulatory Effects

Abstract The noncoding genome presents a largely untapped source of biological insights, including thousands of long noncoding RNA (lncRNA) loci. While some produce bona fide lncRNAs, others exert transcript-independent cis-regulatory effects, and the lack of predictive features renders mechanistic dissection challenging. Here, we describe CTCF-enriched lncRNA loci (C-LNC) as a subclass of functional genetic elements exemplified by MYNRL15, a pan-myeloid leukemia dependency identified by an lncRNA-based CRISPRi screen. MYNRL15 perturbation selectively impairs acute myeloid leukemia (AML) cells over hematopoietic stem / progenitor cells in vitro, and depletes AML xenografts in vivo. Mechanistically, we show that crucial DNA elements in the locus mediate its phenotype, triggering chromatin reorganization and downregulation of cancer dependency genes upon perturbation. Elevated CTCF density distinguishes MYNRL15 and 531 other lncRNA loci in K562 cells, of which 43-54% associate with clinical aspects of AML and 18.4% are functionally required for leukemia maintenance. Curated C-LNC catalogs in other cell types will help refine the search for noncoding oncogenic vulnerabilities in AML and other malignancies.

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